The overall goal of this proposal is to develop a minimally-invasive optical imaging technology for the diagnosis of kidney diseases in vivo and in real time. Specifically, in this Pilot and Feasibility Clinical Research Grants in Kidney or Urologic Diseases (R21), we will image the ischemic injury in human subjects during laparoscopic partial nephrectomy procedures to investigate the feasibility of quantitative imaging of the kidney's morphological and functional parameters for assessment of the extent of injury in vivo using multi-parameter optical imaging. Acute kidney injury (AKI) represents a common and potentially devastating disease in clinical medicine with high mortality and morbidity rate. Currently, there is no objective tool for the early diagnosis and real time assessment of the status of AKI. However, timely and appropriate interventions are essential to the potential success and outcome of a therapy. Therefore, there is a critical need for developing new diagnostic tools which can assess the severity and extent of AKI, quantify the physiological parameters of disease, and evaluate disease progression or response to therapy, in vivo and in real time. Such a technology would represent a major advance in the diagnosis and treatment of kidney diseases. This proposal is built upon our unique multi-modal optical imaging platform combining high-resolution optical coherence tomography (OCT) and high-sensitivity fluorescence imaging for simultaneous structural and functional imaging. Our extensive preliminary data on both animal and human kidneys demonstrate the strong potential and promise for optical imaging of kidney pathology. Specifically, we have demonstrated that OCT can provide high-resolution images of the intact human kidney structures including vessels, tubules, and glomeruli; and fluorescence imaging can monitor the dynamics of the glomerular filtration. Together, multi- modal optical imaging provides comprehensive assessment of kidney structural and functional status for more accurate diagnosis and prognosis. To translate this new technology from bench to bedside, we propose to pursue the following three specific aims: 1) Develop a laparoscopic imaging probe for multi-parametric optical imaging of kidney structure and function in vivo. 2) Validate the performance of minimally-invasive multi- parametric imaging on animal model of kidney ischemia. 3) Translate the laparoscopic multi-parametric optical imaging to image human kidney structure and function in vivo during standard laparoscopic procedures. By the end of this proposal, the new minimally-invasive multi-parameter optical imaging technology will be fully developed and its clinical feasibility will be validated. This technology should be ready for the next step larger scale clinical study. This technology will open a new avenue for diagnosis and treatment of kidney diseases including AKI, improve the life quality of patients suffering from these diseases, and positively impact health care throughout the United States.